Holoprosencefalia lobar en un recién nacido / Lobar Holoprosencephaly in A Newborn Infant

Introducción: La holoprosencefalia es la consecuencia directa de cambios genéticos o ambientales específicos que interrumpen la división de la línea media del prosencéfalo embrionario o prosencéfalo. Estas alteraciones pueden condicionar disímiles alteraciones fenotípicas en los seres humanos. Objetivo: Describir las manifestaciones clínicas de pacientes con holoprosencefalia y la conducta clínica y terapéutica en un neonato. Presentación del caso: Hijo de padres no consanguíneos, madre de 35 años de edad con antecedente de cervicitis y gestorragia en la segunda mitad del embarazo, y antecedentes familiares de diabetes mellitus y cardiopatía. El parto se produjo a término a las 37 semanas, distócico por cesárea secundaria a un hematoma retroplacentario. Se obtuvo un recién nacido del sexo masculino con presentación pelviana, peso de 3380 gramos y Apgar 9/9 al nacer. La cesárea se realizó en el Hospital Materno Sur Mariana Grajales Coello (área urbana) de Santiago de Cuba. En el recién nacido se observaron rasgos dismórficos principalmente cráneo-facial. No precisó reanimación, pero a los pocos minutos comenzó con cuadro de dificultad respiratoria e hiposaturación. Conclusiones: En la holoprosencefalia el diagnóstico posnatal se puede realizar mediante las características fenotípicas, las malformaciones faciales y los estudios neuroimagenológicos como el ultrasonido transfontanelar y la tomografía axial computarizada de cráneo. Los pacientes deben evaluarse y seguirse en la evolución por un equipo multidisciplinario de especialidades como otorrinolaringología, máxilo-facial, neuropediatría, consulta de neurodesarrollo, genética, fisiatría e imagenología(AU)

Introduction: Holoprosencephaly is the direct consequence of specific genetic or environmental changes that disrupt midline division of the embryonic prosencephalon or prosencephalon. These alterations can condition dissimilar phenotypic alterations in humans. Objective: To describe the clinical manifestations of patients with holoprosencephaly and the clinical and therapeutic behavior in a neonate. Case presentation: Child of non-consanguineous parents, 35-year-old mother with a history of cervicitis and gestation bleeding in the second half of pregnancy, and family history of diabetes mellitus and heart disease. Delivery was at term, at 37 weeks, dystocic by cesarean section secondary to a retroplacental hematoma. The result was a male newborn with breech presentation, weight 3380 grams and Apgar 9/9 at birth. The cesarean section was performed at the Hospital Materno Sur Mariana Grajales Coello (urban area) of Santiago de Cuba. Dysmorphic features were observed in the newborn, mainly craniofacial dysmorphic ones. He did not require resuscitation, but a few minutes later he presented respiratory distress and hyposaturation. Conclusions: In holoprosencephaly, postnatal diagnosis can be made by phenotypic features, facial malformations and neuroimaging studies such as transfontanellar ultrasound and cranial computed tomography. Patients should be evaluated and followed in evolution by a multidisciplinary team of specialties such as otorhinolaryngology, maxillofacial, neuropediatrics, neurodevelopmental consultation, genetics, physiatry and imaging(AU)

Holoprosencephaly in Patau Syndrome / Holoprosencefalia na Síndrome de Patau

ABSTRACT Objective: To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies. Case description: This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis. Comments: Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.

RESUMO Objetivo: Avaliar sinais radiológicos (gestacionais e perinatais) e neonatais de paciente com síndrome de Patau e holoprosencefalia semilobar, assim como relatar a associação de ambas as patologias. Descrição do caso: Trata-se de um relato de recém-nascido do sexo feminino a termo, que apresentou trissomia do cromossomo 13 e holoprosencefalia semilobar, com fusão talâmica e ventrículo cerebral único, além de várias outras alterações que pioraram o prognóstico da paciente. Comentários: A trissomia do cromossomo 13 é um defeito genético que caracteriza um conjunto de sintomas que compõem a Síndrome de Patau. Nesta síndrome, é comum o acometimento cardiovascular, urogenital, do sistema nervoso central, da estrutura facial e da capacidade intelectual, além de falhas na formação dos membros, como diminuição no comprimento do úmero, fêmur, polidactilia, hipotelorismo e baixa implantação das orelhas. Estima-se, no entanto, que a holoprosencefalia apresente-se nesse grupo de malformações congênitas apenas em 24 a 45% dos casos.

The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI.

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.

Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal / The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI

Las anomalías congénitas del sistema nervioso central constituyen un amplio grupo de malformaciones asociadas a una gran variedad de síndromes genéticos y anomalías cromosómicas, y una de las principales causas de morbimortalidad infantil. Dentro de ellas, la holoprosencefalia conlleva un trastorno de la diferenciación del prosencéfalo, con una falta completa o parcial de división entre los hemisferios cerebrales. Para su diagnóstico prenatal es fundamental la realización de pruebas de imagen y el conocimiento de los posibles hallazgos, debido a que su pronóstico es variable, comenzando normalmente con la ecografía y confirmando lo visualizado con la resonancia magnética.(AU)

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.(AU)

Diabetis insípida associada a holoprosencefàlia / Diabetes insípida asociada a holoprosencefalia / Diabetes insipidus associated with holoprosencephaly

Introducció. L’holoprosencefàlia és una malformació congènita greu que compromet estructures cerebrals situades ala línia mitjana. Per la seva localització, l’hipotàlem i lahipòfisi són estructures afectades sovint en aquesta entitat. La seva disfunció pot provocar trastorns de l’homeòstasii endocrinopaties com l’adípsia i la diabetis insípida.Cas clínic. Es presenta el cas d’una nena de 6 anys diagnosticada d’holoprosencefàlia als 9 mesos de vida. Consulta per somnolència i febre de 48 hores d’evolució i enl’exploració presenta signes de deshidratació. La mare refereix que no reclama ingesta hídrica tot i trobar-se deshidratada. Analíticament destaca deshidratació hipernatrèmica greu amb disfunció renal. A les 72 hores d’ingrés,després d’haver corregit les diselectrolitèmies i amb lapacient normohidratada, reapareix la hipernatrèmia ambpoliúria i osmolalitat urinària disminuïda. Es fa un test dedesmopressina que confirma la sospita diagnòstica de dèficit d’hormona antidiürètica associat a adípsia. S’instauratractament amb desmopressina i restricció hídrica amb elqual s’assoleix un bon control hidroelectrolític que esmanté en controls posteriors.Comentaris. Els pacients amb holoprosencefàlia tenen riscde presentar endocrinopaties per disfunció hipotalamohipofisiària. Per aquest motiu cal buscar-les activament encas de presentar-se la clínica clàssica de poliúria, hipernatrèmia i hipoosmolalitat urinària. (AU)

Introducción. La holoprosencefalia es una malformación congénitagrave que compromete estructuras cerebrales situadas en la líneamedia. Por su localización, el hipotálamo y la hipófisis son estructuras frecuentemente afectadas en esta entidad. Su disfunciónpuede generar trastornos de la homeostasis y endocrinopatíascomo la adipsia y la diabetes insípida.Caso clínico. Se presenta el caso de una niña de 6 años diagnosticada de holoprosencefalia a los 9 meses de vida. Consulta por somnolencia y fiebre de 48 horas de evolución y en la exploración físicadestacan signos de deshidratación. La madre refiere que no reclama ingesta hídrica pese a encontrarse deshidratada. Analíticamente destaca deshidratación hipernatrémica grave y disfunciónrenal. A las 72 horas de ingreso, corregidas las diselectrolitemias yencontrándose la paciente normohidratada, reaparece hipernatremia asociando poliuria e hipoosmolalidad urinaria. Se realiza untest de desmopresina que confirma la sospecha diagnóstica de déficit de hormona antidiurética asociado a adipsia. Se instaura tratamiento con desmopresina y restricción hídrica, alcanzando un buencontrol hidroelectrolítico que mantiene en controles posteriores.Comentarios. Los pacientes con holoprosencefalia tienen riesgo depresentar endocrinopatías por disfunción hipotálamo-hipofisaria.Por ese motivo es necesario buscarlas activamente en caso depresentarse la clínica clásica de poliuria, hipernatremia e hipoosmolalidad urinaria. (AU)

Introduction. Holoprosencephaly is a severe developmental defectthat compromise midline brain structures. Due to their location,the hypothalamus and the hypophysis are frequently involvedin this illness. Their dysfunction can lead to homeostatic andendocrine disorders such as thirst disturbances and diabetesinsipidus.Case report. Herein we report the case of a 6-year-old girl who wasdiagnosed with holoprosencephaly at 9 months old. She presentedwith a 48-hours history of somnolence and fever with signs of dehydration on examination. Her mother stated that despite beingdehydrated, she did not demand water intake. Laboratory evaluation revealed a severe hypernatremic dehydration with renal impairment. Seventy-two hours after admission, having successfullyattained fluid and electrolyte correction, she presented hypernatremia with polyuria and urine hypoosmolality. A desmopressin testwas performed confirming the suspected diagnosis of antidiuretichormone deficiency and adipsia. She responded well to desmopressin treatment and fluid restriction with restoration of serumelectrolytes, which remained within acceptable limits at follow-up.Discussion. Children with holoprosencephaly are at risk for endocrine disorders related to hypothalamic-pituitary dysfunction. It isimportant to rule out these disturbances if they present with theclassic triad of hypernatremia, polyuria and urine hypoosmolality. (AU)

The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI. / Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal.

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.

Holoprosencefalia semilobar y malformaciones asociadas: reporte de caso y algunas consideraciones / Semilobar holoprosencephaly and associated malformations: case report and some considerations

RESUMEN: El defecto más común del prosencéfalo es la holoprosencefalia (HPE), caracterizada por ausencia en la división del prosencéfalo. La holoprosencefalia tiene una prevalencia de 1/10.000 en recién nacidos; la ciclopía de 1/100.000 nacidos y la agnatia asociada a holoprosencefalia de 0,8 a 10 %. El objetivo fue describir las características morfológicas e histopatológicas de un feto humano con holoprosencefalia y sus malformaciones asociadas. Se estudió un feto masculino. Se le realizó microdisección bajo el estereomicroscopio, toma de microfotografías con cámara AxioCam y software AxioVision 4.8, y estudio histopatológico. La edad gestacional estimada fue de 12,4-13,2 semanas, encontrándose como hallazgos la HPE semilobar asociada a ciclopía, esbozo oral hipoplásico sin apertura oral, cubierta por una membrana y ausencia de labios. El estudio histopatológico reportó: ojo con lente, retina y córnea únicos; en la cara, probóscide con cartílago tubular en formación asociado a mesénquima y cubierta muscular esquelética, y cavidad oral pequeña, circunscrita por mandíbula hipoplásica conformada por cartílago. Se revisa la literatura y se reafirma la necesidad de estudio multidisciplinario de esta patología para mejorar su comprensión.

SUMMARY: The most common defect of the forebrain is holoprosencephaly (HPE), characterized by absence in the forebrain division. Holoprosencephaly has a prevalence of 1 / 10,000 in newborns; the cyclopia of 1 / 100,000 births and the agnathia, in a series of cases of holoprosencephaly ranges from 0.8 to 10 %. The objective was the description of the morphological and histopathological characteristics of fetus with holoprosencephaly and its associated malformations. A male fetus was studied. Microdissection was performed under the stereomicroscope, taking microphotographs with AxioCam camera and AxioVision 4.8 software, and histopathological study. The estimated gestational age was 12.4-13.2 weeks, the findings were semilobar HPE, associated with cyclopia, hypoplastic oral outline without buccal opening, covered by a membrane and lips absence. The histopathological study reported: eye with lens, retina and cornea only; in the face, proboscis with tubular cartilage in formation associated with mesenchyme and musculoskeletal sheath, and small oral cavity, delimited by hypoplastic mandible conformed by cartilage. The literature is reviewed and reaffirmed the need for multidisciplinary studies of this disease to improve their understanding.

Incisivo central único de la línea media del maxilar, holoprosencefalia y estenosis congènita del orificio nasal anterior en un recién nacido prematuro: a propósito de un caso / Solitary median maxillary central incisor, holoprosencephaly and congenital nasal pyriform aperture stenosis in a premature infant: case report

El síndrome del incisivo central único de la línea media del maxilar es un trastorno raro que implica anomalías de la línea media, como holoprosencefalia, anomalías de las fosas nasales, fisura palatina, labio leporino, hipotelorismo, microcefalia y panhipopituitarismo. La estenosis congénita del orificio nasal anterior es una causa mortal de dificultad respiratoria neonatal debido al estrechamiento del orificio nasal anterior, y podría confundirse con la atresia de coanas. En este informe, presentamos el caso de un recién nacido con síndrome del incisivo central único de la línea media del maxilar acompañado de otras anomalías, tales como holoprosencefalia, estenosis del orificio nasal anterior, microcefalia y panhipopituitarismo. El cariotipado mostró una deleción heterocigota en el gen SIX3 en la región 2p21, que produjo una forma más grave de holoprosencefalia.

Solitary median maxillary central incisor syndrome is a rare disorder involving midline abnormalities such as holoprosencephaly, nasal cavity anomalies, cleft palate-lip, hypotelorism, microcephaly, and panhypopituitarism. Congenital nasal pyriform aperture stenosis is a lethal cause of neonatal respiratory distress due to narrowing of the pyriform aperture anteriorly and it can be confused with choanal atresia. In this report, we present a newborn infant with solitary median maxillary central incisor syndrome accompanied by other abnormalities including holoprosencephaly, nasal pyriform aperture stenosis, microcephaly and panhypopituitarism. Chromosomal analysis showed heterozygous SIX3 gene deletion at 2p21 region resulting in a more severe form of holoprosencephaly.

Atención odontológica a un bebé con holoprosencefalía: relato de caso clínico / Dental care for a baby with holoproscephaly: case report

Ejercer el rol de cuidador de un niño con deformaciones congénitas es una tarea difícil y representa un componente importante dentro de la familia en tanto que esa persona se hace responsable del cuidado de ese ser especial. Para que esto suceda, la conducta de los profesionales del área de la salud frente a este contexto debe ser específica y de calidad, de modo a ofrecer el soporte necesario a la familia/cuidador. Con el fin de promover una atención efectiva, los profesionales deben buscar el conocimiento del síndrome que afecta al paciente, así como su respuesta conductual y sus características mas prevalentes. El presente trabajo tuvo como objetivo presentar el informe de un caso clínico de un paciente bebé del sexo femenino, que requiere de cuidados exclusivos por parte de sus padres, quienes buscaron asistencia en la Universidad Federal de Río Grande do Sul, Brasil, en la disciplina Atención Odontológica al Paciente Necesidades Especiales. También se hace hincapié en el manejo y los cuidados por parte del odontólogo de aquellos pacientes con discapacidad desde el momento de su nacimiento, a fin de proporcionarles los recursos adecuados a través de orientaciones en cuanto a la higiene bucal con el fin de que se pueda instalar y mantener las condiciones de la salud oral, mejorando la calidad de vida de los pacientes con discapacidad.

The exercise the role of caregiver of a child with birth defects is a difficult task and takes a significant role in the family, to the extent that this person actually wants to become responsible for the care that is why the conduct of health professionals within this context must be specific and quality, in order to provide the necessary support to the family/caregiver.To be able to give an effective care, the professionals must seek knowledge of the syndromes that affect the patients, as well as their behavioral response and their common features. The aimed of this study is to present a case report about a female baby, with disabilities whichinvolve several malformations, including a delay in the normal development and demand undivided care by her parents, who looked for professional care with prevent purpose on the subject named: Atendimento Odontológico ao Paciente com Necessidades Especiais, in the Federal University of Rio Grande do Sul. In addition, this paper has the purpose, to call the attention to the handling and care that should be taken in relation to those with disabilities since the moment of his birth by the dentist, providing them, with appropriate means through guidance on the oral hygiene with the purpose of to install and maintain adequate oral health conditions, improving the quality of life for patients with disabilities.

Polidactilia, holoprosencefalia, labio y paladar hendido: no siempre es lo que parece / Polydactyly, holoprosencephaly, cleft lip and cleft palate are not always what they seem: Case report

Reportamos un neonato masculino con defectos de línea media, cardiopatía congénita y polidactilia, características sugestivas de trisomía 13. Sin embargo, el reporte de cariotipo fue normal. Por hallazgos clínicos, el diagnóstico final probable fue pseudotrisomía 13. Aunque el pronóstico de ambas condiciones es pobre, los estudios genéticos siempre son necesarios para establecer una adecuada asesoría genética. Si bien hay síndromes con presentación similar, como el de Meckel, el de Smith-Lemli- Opitz, el de Pallister-Hall y el hidroletalus, se puede realizar una aproximación diagnóstica basada en los antecedentes perinatales, el peso al nacer, el tiempo de supervivencia y algunos rasgos característicos de cada síndrome. Además, pueden existir, en algunos países, limitaciones para realizar estudios genéticos, por lo que los criterios clínicos pueden ser relevantes.

We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.

Correlation of bispectral index (BIS) monitoring and end-tidal sevoflurane concentration in a patient with lobar holoprosencephaly / Correlação entre monitoração do índice bispectral (BIS) e concentração expirada de sevoflurano em paciente com holoprosencefalia lobar

ABSTRACTOBJECTIVE: The bispectral index (BIS) is a parameter derived by electroencephalography (EEG) which provides a direct measurement of the effects of sedatives and anesthetics on the brain and offers guidance on the adequacy of anesthesia. The literature lacks studies on BIS monitoring in pediatric patients with congenital brain disease undergoing general anesthesia.CLINICAL FEATURES: A 13-year-old child weighing 32 kg, suffering from lobar holoprosencephaly, underwent surgery in which the bispectral index (BIS) monitoring the depth of anesthesia showed an abnormal response. Detailed analysis of the trends of BIS values in the different observation times demonstrated sudden falls and repetitive values of BIS likely related to repetitive epileptiform electrical activity caused by sevoflurane.CONCLUSION: The BIS is a very useful monitoring tool for assessing the degree of depth of anesthesia and to analyze the electroencephalographic variations of anesthetics. Particular attention should be given to patients with congenital disorders of the central nervous system in which the BIS may give abnormal responses that do not reflect an accurate assessment of the depth of anesthesia.

RESUMOOBJETIVO: O índice bispectral (BIS) é um parâmetro derivado por eletroencefalografia (EEG) que fornece uma medida direta dos efeitos de sedativos e anestésicos no cérebro e orientação sobre a adequação da anestesia. A literatura carece de estudos sobre a monitoração do BIS em pacientes pediátricos com doença cerebral congênita submetidos à anestesia geral.CARACTERÍSTICAS CLÍNICAS: Criança de 13 anos de idade, pesando 32 kg, com holoprosencefalia lobar, foi submetida à cirurgia em que a monitoração da profundidade da anestesia com o uso do BIS mostrou uma resposta anormal. A análise detalhada das tendências dos valores do BIS nos diferentes tempos de observação mostrou quedas súbitas e valores repetitivos do BIS, provavelmente relacionados à atividade elétrica epileptiforme repetitiva causada por sevoflurano.CONCLUSÃO: O BIS é uma ferramenta de monitoração muito útil para avaliar o grau de profundidade da anestesia e as variações eletroencefalográficas dos anestésicos. Atenção especial deve ser dedicada aos pacientes com doenças congênitas do sistema nervoso central nos quais o BIS pode apresentar respostas anormais que não refletem a avaliação precisa da profundidade da anestesia.

Polidactilia, holoprosencefalia, labio y paladar hendido: no siempre es lo que parece / Polydactyly, holoprosencephaly, cleft lip and cleft palate are not always what they seem: Case report

Reportamos un neonato masculino con defectos de línea media, cardiopatía congénita y polidactilia, características sugestivas de trisomía 13. Sin embargo, el reporte de cariotipo fue normal. Por hallazgos clínicos, el diagnóstico final probable fue pseudotrisomía 13. Aunque el pronóstico de ambas condiciones es pobre, los estudios genéticos siempre son necesarios para establecer una adecuada asesoría genética. Si bien hay síndromes con presentación similar, como el de Meckel, el de Smith-Lemli- Opitz, el de Pallister-Hall y el hidroletalus, se puede realizar una aproximación diagnóstica basada en los antecedentes perinatales, el peso al nacer, el tiempo de supervivencia y algunos rasgos característicos de cada síndrome. Además, pueden existir, en algunos países, limitaciones para realizar estudios genéticos, por lo que los criterios clínicos pueden ser relevantes.(AU)

We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.(AU)

Correlation of bispectral index (BIS) monitoring and end-tidal sevoflurane concentration in a patient with lobar holoprosencephaly.

OBJECTIVE: The bispectral index (BIS) is a parameter derived by electroencephalography (EEG) which provides a direct measurement of the effects of sedatives and anesthetics on the brain and offers guidance on the adequacy of anesthesia. The literature lacks studies on BIS monitoring in pediatric patients with congenital brain disease undergoing general anesthesia. CLINICAL FEATURES: A 13-year-old child weighing 32kg, suffering from lobar holoprosencephaly, underwent surgery in which the bispectral index (BIS) monitoring the depth of anesthesia showed an abnormal response. Detailed analysis of the trends of BIS values in the different observation times demonstrated sudden falls and repetitive values of BIS likely related to repetitive epileptiform electrical activity caused by sevoflurane. CONCLUSION: The BIS is a very useful monitoring tool for assessing the degree of depth of anesthesia and to analyze the electroencephalographic variations of anesthetics. Particular attention should be given to patients with congenital disorders of the central nervous system in which the BIS may give abnormal responses that do not reflect an accurate assessment of the depth of anesthesia.

[Correlation of bispectral index (BIS) monitoring and end-tidal sevoflurane concentration in a patient with lobar holoprosencephaly]. / Correlação entre monitoração do índice bispectral (BIS) e concentração expirada de sevoflurano em paciente com holoprosencefalia lobar.

OBJECTIVE: The bispectral index (BIS) is a parameter derived by electroencephalography (EEG) which provides a direct measurement of the effects of sedatives and anesthetics on the brain and offers guidance on the adequacy of anesthesia. The literature lacks studies on BIS monitoring in pediatric patients with congenital brain disease undergoing general anesthesia. CLINICAL FEATURES: A 13-year-old child weighing 32kg, suffering from lobar holoprosencephaly, underwent surgery in which the bispectral index (BIS) monitoring the depth of anesthesia showed an abnormal response. Detailed analysis of the trends of BIS values in the different observation times demonstrated sudden falls and repetitive values of BIS likely related to repetitive epileptiform electrical activity caused by sevoflurane. CONCLUSION: The BIS is a very useful monitoring tool for assessing the degree of depth of anesthesia and to analyze the electroencephalographic variations of anesthetics. Particular attention should be given to patients with congenital disorders of the central nervous system in which the BIS may give abnormal responses that do not reflect an accurate assessment of the depth of anesthesia.

Holoprosencefalia: a proposito de un caso / Holoprosencephaly: report a case

Se reporta el caso de una mujer de 22 años de edad, sin antecedentes de importancia. Fue admitida en el hospital, enpródromos de trabajo de parto, gestación de 40 semanas y malformación cerebral: holoprosencefalia semilobar, hipotelorismo, hidronefrosis derecha leve (diagnóstico ecográfico). Es intervenida mediante la operación cesáreaobteniéndose un recién nacido con características de holoprosencefalia siendo lo resaltante el hipotelorismo y laarrinencefalia. No presenta llanto al nacimiento, por lo que se le realiza maniobras de reanimación cardio pulmonar, continùaen mal estado general con periodos de apnea, baja saturación, expansibilidad torácica disminuida, se procede a colocaciónde tubo endotraqueal, administración de adrenalina, es llevada al servicio de unidad de cuidados intensivos pediátricos,presentando en el trayecto dos episodios de paro cardiaco, el menor luego es colocado en ventilador mecánico, no teniendouna buena evolución ,fallece el día siguiente de nacido.

It is reported the case of a woman, 22 years of age, without important background information. She was admitted to the hospital, in premonitory signs of 40 weeks and cerebral malformation: semilbar holoprosencephaly, hipotelorismo, mild right hydronephrosis (sonographic diagnosis). She is operated by the cesarean section obtaining a newborn with characteristics of holoprosencephaly remains what the striking hipotelorismo and arrinencefalia. There is no crying at birth, by what is realized maneuvers cardio pulmonary resuscitation, continues un poor condition general, with periods of apnea, low saturation, chest diminished expansibility, so proceeded to endotracheal tube placement, placement of adrenaline, is taken to the pediatric intensive care units, presenting in the journey two episodes of cardiac arrest, the minor then is placed on mechanical ventilator, not taking a good evolution, dies the net day of birth.

Use of 3D multislide CT in the study of a fetus with cyclopia / Utilización de TC multicorte 3D en el estudio de un feto con ciclopia

Cyclopia is a rare congenital malformation incompatible with life; it is characterized by the presence of a single eye in the center position, secondary to alobar holoprosencephaly. Cyclopia etiology is heterogeneous, with a prevalence of 1.05 in 100,000 births. We report a case of cyclopia with sinoftalmía in a fetus of 21 weeks where they use 3D multislice computed tomography as a complementary study.

La ciclopía es una malformación congénita rara e incompatible con la vida, caracterizada por la presencia de un solo ojo en posición central, secundaria a holoprosencefalia alobar. La ciclopía es de etiología heterogénea, con una prevalencia de 1,05 en 100000 nacimientos. Presentamos un caso de ciclopía con sinoftalmía en un feto de 21 semanas en donde se utilizo tomografía computarizada multicorte 3D como estudio complementario.

Genomic imbalances detected through array CGH in fetuses with holoprosencephaly / Instabilidades genômicas detectadas através de array CGH em fetos com holoprosencefalia

OBJECTIVE: Holoprosencephaly (HPE) is heterogeneous in pathogenesis, integrating genetic susceptibility with the influence of environmental factors. Submicroscopic aberrations may contribute to the etiology of HPE. Our aim was to report the molecular analysis of 4 fetuses with HPE and normal metaphase karyotype. METHOD: A whole genome BAC-array based Comparative Genomic Hybridization (array CGH) was carried out in fetal blood samples. All potential cytogenetic alterations detected on the arrays were matched against the known copy number variations databases. RESULTS: The array CGH analysis showed copy number gains and losses in all cases. We found a recurrent deletion in 15q14 (clone RP11-23J11) and in 15q22 (clone RP11-537k8) in 2 out 4 cases analyzed. We also observed submicroscopic gain in 6p21 in 3 out of 4 fetuses in nearby clones. All these regions were tested in known databases and no copy number variations have been described for them. CONCLUSION: This is the first report of molecular characterization through a whole genome microarray CGH of fetuses with HPE. Our results may contribute to verify the effectiveness and applicability of the molecular technique of array CGH for prenatal diagnosis purposes, and contributing to the knowledge of the submicroscopic genomic instability characterization of HPE fetuses.

OBJETIVO: Holoprosencefalia (HPE) é uma malformação heterogênea na patogênese, integrando a suscetibilidade genética com a influência de fatores ambientais. Aberrações submicroscópicas podem contribuir para a etiologia da HPE. Nosso objetivo foi relatar a análise molecular de 4 fetos com HPE e cariótipo normal. MÉTODO: Foi realizado um estudo descritivo prospectivo dos achados da técnica de hibridação genômica comparativa baseada em microarranjos utilizando BAC clones de ampla cobertura genômica (BAC-array CGH) em amostras sanguíneas de fetos portadores de holoprosencefalia e com cromossomos numericamente normais ao bandamento G. Todas as potenciais alterações citogenéticas detectadas foram comparadas com bancos de dados com variações do número de cópias conhecidas. RESULTADOS: A análise de array CGH evidenciou ganhos e perdas do número de cópias em todos os 4 casos. Foram encontradas deleções recorrentes em 15q14 (clone RP11-23J11) e em 15q22 (clone RP11-537k8) em 2 dos 4 casos analisados. Observou-se em 3 fetos ganho genômico na região 6p21 em clones próximos. Todas estas regiões não apresentaram variações do número de cópias descritas em bancos de dados conhecidos. CONCLUSÃO: Este é o primeiro relato de caracterização molecular através de um microarray CGH de fetos com HPE. Nossos resultados podem contribuir para verificar a eficácia e aplicabilidade da técnica molecular de array CGH para fins de diagnóstico pré-natal, contribuindo para o conhecimento da caracterização de instabilidades genômicas submicroscópicas de fetos com HPE.

18p- syndrome: presentation of two cases with alobar holoprosencenphaly / Síndrome 18p-: presentación de dos casos con holoprosencefalia alobar

Introduction: The syndrome by deletion of the short arm of chromosome 18 is an infrequent syndrome, and its phenotypical variability makes it difficult to recognize. Its most frequently observed clinical characteristics include mental retardation, growth retardation, craniofacial malformations, including long ears, microcephaly and short neck; other less frequent associated malformations include holoprosencephaly. Case report: We present two patients with deletion of the short arm of chromosome 18, one presented a de novo mutation and the other was produced by a balanced translocation 6p/18p of maternal origin. Both patients presented alobar holoprosencephaly and cebocephaly, low-frequency clinical characteristics in this syndrome. Discussion: alobar holoprosencephaly is a malformation appearing in 10% of patients with deletion of the short arm of chromosome 18; we review the probable physiopathology of holoprosencephaly in this syndrome.

Introducción: El síndrome por deleción del brazo corto del cromosoma 18, es un síndrome poco frecuente y su variabilidad fenotípica lo hace difícil de reconocer. Las características clínicas observadas con más frecuencia incluyen retardo mental y de crecimiento, malformaciones craneofaciales que incluyen orejas largas, microcefalia y cuello corto; otras malformaciones asociadas menos frecuentes incluyen la holoprosencefalia. Reporte de casos: Se presentan dos pacientes con deleción del brazo corto del cromosoma 18, uno presentado de novo y otro producido por translocación balanceada 6p/18p de origen materno. Ambos pacientes presentaron holoprosencefalia alobar y cebocefalia, características clínicas de baja frecuencia en este síndrome. Discusión: La holoprosencefalia alobar es una malformación que se presenta en 10% de los pacientes con deleción del brazo corto del cromosoma 18; se revisa la probable fisiopatología de la holoprosencefalia en este síndrome.

Síndrome de incisivo central superior mediano: relato de caso / Syndrome of the single median maxilarry central incisor: case report

A síndrome do incisivo central superior mediano inclui uma variedade de sinais clínicos decorrentes de defeitos de desenvolvimento das estruturas medianas da face e da parte anterior do cérebro. A agenesia de um dos incisivos centrais superiores é um dos sinais clínicos que caracteriza essa síndrome e, por se tratar de anomalia presente na cavidade bucal, institui o cirurgião dentista como um dos primeiros profissionais a ter contato com esses pacientes. O presente trabalho tem por objetivo apresentar um paciente com tal síndrome, buscando promover o embasamento dos profissionais para que estejam qualificados a diagnosticar, orientar e tratar esses pacientes.

Descripción clínica y anatomopatológica de dos casos de holoprosencefalia / Clinical and antomopathologycal description of two holoproscencephaly cases

La holoprosencefalia es una de las más graves y la más común de las malformaciones cerebrales y faciales; consiste en la diverticulación nula o incompleta del prosencéfalo embrionario hacia los hemisferios cerebrales y ventrículos laterales; se acompaña de defectos en las estructuras de la línea media como boca y nariz, es de aparición temprana en el desarrollo del sistema nervioso central y ocurre como consecuencia de una posible falla en un conjunto de moléculas, que incluyen la proteína Sonic Hedgehog y a la superfamilia de genes BMP, indispensables para la formación normal del encéfalo; además, se ha asociado con anomalías en los cromosomas 13, 3, 7 y 18. Hasta el momento, el diagnóstico y clasificación es anatomopatológico. Se describen dos casos de la variante semilobar diagnosticados por ecografía, y posteriormente por necropsia. El objetivo de este artículo es exponer dichos casos y hacer una breve descripción del mecanismo fisiopatológico implicado...

The holoproscencephaly is one of the most serious and common among the facial and brain malformations; it consists in the incomplete or null diverticulation of the embrionary prosencefalus through the brain hemispheres and lateral ventricles; is accompanied by defects of the middle line structures, as mouth and nose, it has and early showing in the development of the central nervous system, and it occurs as a consequence of a possible failure over a set of molecules, that include the Sonic Hedgehog protein, and the superfamily genes BPM, indispensable to the normal formation of the encephalon, moreover it has been associated with anomalies over the 13, 3, 7 and 18 chromosomes. Till now, the diagnostic and classifi cation is anatomic-pathologic. It describes two cases of the semilobar diagnostic by ecography, and later bynecropsy. The objective of this article is to expose thy cases and done a brief description of the physiopathology involve mechanism...